Bromine → 5-(2-Fluoro-4-pyridyl)-4-(3-methylphenyl)-2-[4-(methylthio)phenyl]-1,3-thiazole

HRID 2212342Notes

Reaction equation

HRID 2212342 reaction equation
BrBr.[F:3][C:4]1[CH:9]=[C:8]([CH2:10][C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=2)=O)[CH:7]=[CH:6][N:5]=1.[CH3:20][S:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([NH2:28])=[S:27])=[CH:24][CH:23]=1.C(=O)([O-])O.[Na+]>C(O)(=O)C>[F:3][C:4]1[CH:9]=[C:8]([C:10]2[S:27][C:26]([C:25]3[CH:29]=[CH:30][C:22]([S:21][CH3:20])=[CH:23][CH:24]=3)=[N:28][C:11]=2[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=2)[CH:7]=[CH:6][N:5]=1

Participants

6

Reactant 4

HCID 24408BromineHCID 516892Sodium BicarbonateHCID 30033144-(Methylthio)thiobenzamideHCID 115431572-(2-Fluoro-4-pyridyl)-1-(3-methylphenyl)ethanone

Product 1

HCID 101573605-(2-Fluoro-4-pyridyl)-4-(3-methylphenyl)-2-[4-(methylthio)phenyl]-1,3-thiazoleYield 23%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Bromine (2.7 mL, 52 mmol) was added to a solution of 2-(2-fluoro-4-pyridyl)-1-(3-methylphenyl)ethanone (12 g, 53 mmol) in acetic acid (90 mL) and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated. This residue was dissolved in N,N-dimethylformamide (60 mL), 4-(methylthio)thiobenzamide (9.6 g, 52 mmol) was added and the mixture was stirred at room temperature for 15 hours. A saturated aqueous solution of sodium hydrogencarbonate (100 mL) was poured into the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with water, dried and the solvent was distilled off. The residue was purified by silica gel column chromatography (hexane:ethyl acetate, 4:1) to obtain 4.7 g (yield 23%) of the title compound.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionThis residue was dissolved in N,N-dimethylformamide (60 mL)
  3. stirringthe mixture was stirred at room temperature for 15 hours
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with water
  6. customdried
  7. distillationthe solvent was distilled off
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate, 4:1)

Sources & evidence

ORD record
ord-37b8be9e91674ff8825d2288832fa7e0
Source dataset
uspto-grants-2006_09
Patent number
US07101899B1

Reaction notes

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